Optically active diamino phosphine sulfides

ABSTRACT

Optically active isomers of asymmetrical diamino phosphine sulfides containing a P-imidazolyl radical are resolved and separated.

United States Patent [72] inventors Henry Tolkmith Midland, Mich.; James N. Seiber, Davis, CaliL; Paul B. Budde, Midland, Mich.

[21] Appl. No. 868,595

[22] Filed Oct. 22, 1969 [45] Patented Nov. 16, 1971 [7 3 Assignee The Dow Chemical Company Midland, Mich.

Continuation-impart oi application Ser. No. 604,153, Dec. 23, 1966, now abandoned. This application Oct. 22, 1969, Ser. No. 868,595

[54] OPTICALLY ACTIVE DIAMINO PHOSPHINE SULFIDES 17 Claims, No Drawings 52 03.01;... .I 260/309, 260/551 P, 260/959, 260/960, 424/273 51 Int.Cl ..C07d49/36 50 Field oiSearch 260/309 [56] References Cited UNITED STATES PATENTS 3,323,990 6/1967 Buddeetal 424/27 ABSTRACT: Optically active isomers of asymmetrical diamino phosphine sulfides containing a P-imidazolyl radical are resolved and separated.

OPTICALLY ACTIVE DIAMINO PHOSPI-IINE SULFIDES CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of our copending application Ser. No. 604,153, filed Dec. 23, 1966, and now abandoned.

BACKGROUND OF THE INVENTION Asymmetrical organophosphorus compounds have been the subject of a considerable amount of interest. This interest arises, in a substantial part, from the fact that a great number of organophosphorus compounds exhibit various biological activities, and many such compounds find commercially important application in areas of animal health, crop raising, control of disease-carrying insects, and the like. Representative organophosphorus compounds include, for example, (ethylamino)(4'nitrophenoxy) (amino) phosphine sulfide and (dimethylamino) (4-nitrophen0Xy) (methylamino) phosphine sulfide taught as insecticides in US. Pat. No. 2,552,577; N,N- diethyl N-n-butyl phenyl phosphonodiaminothinoate, useful as a herbicide. P-imidazol-l-yl-N,N-dimethyl-P-phenyl phosphinothioic amide, (diethylamino) phenyl-( 2-methylimidazol-l-yl) phosphine sulfide, P-imidazol-l-yl-N-n-butyl- N-methyl-P-phenyl phosphinothioic amide, (diethylamino) phenyHimidazoH-yl) phosphine sulfide, P-imidazoll-yl- N,N-diethyl-P-phenyl phosphinothioic amide, and other related compounds taught in [1.8. Pat. No. 3,323,990 to be useful as fungicides.

More recently, as the field of organophosphorus chemistry has advanced, there has been increased attention to the mechanisms whereby the various organophosphorus compounds effect the biological activity exhibited. It is in this regard that attention is focused on those biologically active organophosphorus compounds in which the phosphorus atom is asymmetric. In particular, it has been questioned whether either of the enantiomers of such a substance might exhibit a pattern of activity different from the activity otherwise associated with the substance as its known and used racemic mixture; especially since such is true with other known racemic mixtures. Determination of this is dependent upon separation of the enantiomers of the racemic mixture and subsequent separate testing. However, resolution of such racemic mixtures has met with considerable ditficulty, and only a few reactions have been developed. Such methods are, for example, taught by Aaron et al. J.A.C.S. Vol. 80, pages 107-110 and 456-458 (1958), Vol.82, pages 596-598 (1960) and Vol. 84, pages 617-621 (1962); Coyne et al. J.A.C.S. Vol. 78, pages 3061-3063 (1956) and Marsi et al. J.A.C.S. Vol. 78, pages 3,063-3066 (1956). Generally, these reactions require that the organophosphorus compound contain an acidic or basic group which can be reacted with an appropriate resolving agent. Such a group is not found in many commercially important organophosphorus compounds.

Moreover, even when the requisite acidic or basic group is present, many hitherto available resolving methods have been accompanied by limitations, such as difficult procedures and/or low yields. Hence, new methods for the resolution of organophosphorus compounds are needed. Such methods have now been found.

SUMMARY OF THE INVENTION The present invention is directed to a method of resolving and synthesizing asymmetrical diamino phosphine sulfide compounds to separate the optically active enantiomer. The method involves reacting an organophosphorus compound corresponding to the formula (Formula I) with a compound of the formula loweralkyl-Y thereby obtaining an intermediate complex corresponding to the fonnula s towmm mN-i -N' Q ioweralkyl (Formula II) wherein R represents loweralkyl or cyclohexyl; R" represents chloro, nitro or methyl mercapto; 0: represents an integer of from 0 to 2, inclusive; n represents an integer of from 0 to 3, inclusive, and the sum of m+n represents an integer of from 0 to 3, inclusive; and loweralkyl-Y" represents a loweralkyl ester of an optically active camphorsulfonic acid, i.e. Y is an anion of an optically active camphorsulfonic acid.

The intermediate mixture so obtained is separated into its diastereomeric isomers by conventional fractional crystallization. The so separated diastereoisomers are each separately reacted with an alkali metal iodide to obtain an optically active derivative corresponding to the fonnula s (lowmlkynm-i i-n x -iodide loweralkyl (Formula III) The so recovered derivatives, i.e. enantiomers, are thereafter each separately reacted with a nontertiary aminotype compound of the formula wherein R is as hereinbefore defined; to thereby obtain an enantiomer corresponding to the formula 8 /D (lowerelkyl),N--iI -N X 1) (Formula IV) wherein loweralkyl, D and X are as hereinbefore defined.

In the present specification and claims, the term alkali metal is employed to refer to sodium, potassium and lithium, only.

A general reaction scheme of the present process is as fol- 5 lows:

STEP I (loweralkylhN-fl-N loweralkyl-Y -0 l I rl X it Formula I S (loweralkyl),Nil N G e x Formula II R loweralkyl STEP II fractional or stalllzatlon Diastereoisomerlc mixture of Formula II d and Z diastereoisomers of Formula Ia,

STEP III d or I diastoreoisomer of Formula II alkali metal-I izs -I alkali metal-Y s dorI(lowerallryl),Ni -N' l a N I D N alkali metalI lor alkali metalN reactant loweralkyl D Formula IV As is evident from a study of the foregoing, the phosphorus atom in the compounds of formula IV is asymmetric and such compounds have hitherto existed only in a racemic mixture. In accordance with the present invention, however, such compounds can be resolved and synthesized into their enantiomers.

In carrying out this process, the starting compound of formula I, which is a racemic mixture, is reacted with an optically active compound, loweralkylY (step I). In this step, in intermediate mixture corresponding to formula II is prepared, said intermediate exists as a mixture of a pair of 0 diastereoisomers. The mixture of diastereoisomers is resolved to separate each of the optical isomers (step II) and thereafter, each of the separated diastereoisomers is separately reacted with an alkali metal iodide to prepare the iodide complex (step III), which complex exists as the enantiomer. The so prepared complex is reacted with an amino compound as hereinbefore defined to obtain the ultimate optical enantiomeric product (formula IV). This reaction (step IV) with the amino compound results in the breaking of the bond of the phosphorus atom to the nitrogen of the imidazolyl ring and the subsequent preparation of the product of the product of formula IV. This reaction occurs with essentially 100 percent inversion of the enantiomeric form of the asymmetric phosphorus atom. Thus, the ultimate product obtained in such procedures exists in an enantiomeric form which is the inverse of that of the intermediate employed.

In carrying out the present invention, a starting asymmetrical organophosphorus compound of formula I (as a racemic mixture) is contacted with the loweralkyl-Y reactant. Representative loweralkyly reactants include, for example, the loweralkyl adcamphor sulfonates, the loweralkyl 3-a-dcamphor sulfonateand the loweralkyl a-bromocamphor-r-sulfonates.

After the reactants are contacted together, the reaction goes forward readily and gives good yields. The reaction is conveniently carried out in the presence of an inert liquid reaction medium, typically an organic liquid. Suitable such organic liquids include, for example, ether, acetone and secondary alkanols. The reaction consumes the reactants in equimolar amounts, i.e. one molecular proportion of the starting organophosphorus material to one molecular proportion of the loweralkyl-Y reactant, and the employment of the reactants in such amounts, is preferred. The reaction goes forward under temperatures of from 0 to C., but is conveniently carried out at temperatures of from 0 to 50 C.

After the reactants are contacted with one another, the resulting reaction mixture may be held for a period of time following the contacting to insure completion of the reaction. The organophosphorus compound thus produced typically appears in the reaction mixture as a precipitate and is conveniently separated by filtration or decantation. The substance can be used directly in the further practices of the present invention, or can be purified, in conventional procedures, before being so employed.

The intermediate complex mixture of formula II is separated into its diastereoisomers. The separation is carried out in accordance with conventional procedures, typically, by fractional recrystallization from a suitable solvent such as, for example, benzene, cyclohexane or hexane. In many instances, it is convenient to separate only one diastereoisomer. This feature is not necessarily a disadvantage. When it is desired to obtain the other diastereoisomer, it can be obtained by the further practices of the present invention to be hereinafter defined.

After separation, each of the separated diastereoisomers is reacted with an alkali metal iodide which transforms the com plex into an enantiomeric iodide complex. Representative alkali metal iodides include, sodium iodide, potassium iodide and lithium iodide. The so produced enantiomer remains in its respective dextrorotatory or levorotatory form. The reaction conditions for carrying out this step are the same as hereinbefore set forth for preparing the initial complex.

The enantiomeric products of this step are separately reacted with a nontertiary amino-type compound as hereinbefore set forth. Representative amino-type compounds include, for example, ammonia, methylamine, dimethylamine, ethylamine, diethylamine, n-propylarnine, isopropylamine, aniline, Z-ethyIbutyIamine, isobutylamine, or N-heterocyclics and their loweralkyl-substituted compounds including, imidazole, 2-methylimidazole and the N-alkali metal salts of the above compounds.

The following examples illustrate the present invention and will enable those skilled in the art to practice the same.

PREPARATION OF COMPLEXES OF FORMULA II EXAMPLE I dl-(Diethylamino)phenyl(Z-methylimidazol-l-yl)phosphine sulfide (103 grams; 0.35 mole) is mixed with l liter of anhydrous ether and the resulting mixture filtered to remove a small amount of insoluble impurities. Thereupon, 93 grams of methyl a-d-camphorsulfonate (0.40 mole) are added to the filtrate. The addition is carried out at room temperature after completion of the addition, the resulting reaction mixture is heated to reflux temperature, with stirring, and the mixture refluxed for 30 hours with continued stirring. The mixture is cooled to 0 C. and held at that temperature for 2 hours, and filtered to separate the desired dl-(diethyl-amino)phenyl(2- methylirnidazol-l-yl) phosphine sulfide 3-methyl a-dcamphorsulfonate product. The product is washed with anhydrous either (at 0 C.) and dried; the prgductthus obtained melts at l30132.5 C. and represents an 85 percent yield. The specific rotation of this product is found to be [a],, 41.2 (at a concentration of 1.786 grams per 100 milliliters of chloroform). The product is analyzed by nuclear magnetic resonance and the results confirm the identity of the product obtained.

EXAMPLE 2 d1-(Diethylamino)2,4-dichlorophenoxy(Z-methylimidazoll-yl)phosphine sulfide (15.0 grams, 0.04 mole) and diethyl esther 150 milliliters) is stirred in a 2.0-liter 3-necked flask at reflux temperature for 4.0 hours. Methyl S-a-d-camphorsulfonate (10.0 grams, 0.04 mole) in diethyl ether (150 milliliters) is added. With stirring the resulting mixture is heated for 18.0 hours at reflux temperature. The diethyl ether is evaporated off under vacuum. Diethyl ether 100 milliliters) is added to the flask and the contents stirred and heated at reflux for another 18.0 hrs. The solvent is evaporated off and 600: milliliters of diethyl ether is added and the mixture vigorously stirred for 1.0 hr. at room temperature. The insoluble dl-- (diethylamino)2,4-dichlorophenoxy(2-methylimidazole-1- yl)phosphine sulfide 3-methyl a-d-camphorsulfonate is filtered and dried It melts at l07108 C. and the yield is 62.0 percent. The specific rotation of this product is found to be [a],, +29.50 (at a concentration of 0.99 grams per 100 milliliters methanol). The product is analyzed by nuclear magnetic resonance, infrared and elemental analyses to confirm the identity of the product obtained.

A similar preparation in ethyl acetate instead of diethyl ether gives a 76.2 percent yield of product.

EXAMPLE 3 dl-(Diethylamino)2-ehloro-4-t-butylphenoxy(2- methylimidazol-l-yl)phosphine sulfide 3-methylcamphorsulfonate is obtained in a 92.2 percent yield from equivalent molar amounts of dis wiwlzlzq lwn-hu: ty1phenoxy(Z-methylimidazol-1-yl)phosphine sulfide and methyl S-a-d-camphorsulfonate. Preparation is similar to the method described in example 2. dl-(Diethylamino)-2-chloro- 6 PREPARATION OF COMPLEX OF FORMULA lll EXAMPLE 5 10 resulting reaction mixture is swirled until precipitation appeared complete, about 5 minutes, and heated to a temperature of 50 C. and maintained thereat for 30 minutes. The reaction mixture is filtered to remove impure sodium a-dcamphorsulfonate and acetone is removed from the filtrate by evaporation under subatmospheric pressure to obtain the desired l-(diethylamino )phenyl( 2-methylimidazoll yl)phosphine sulfide 3-methyl iodide product. The product is mixed with milliliters of chloroform and the resulting mixture filtered to separate a small amount of additional sodium a-d- 20 camphorsulfonate. The chloroform is removed by evaporation .under subatmospheric pressure and the resulting product iresidue, a glass, is dissolved in 15 milliliters of methanol at lroom temperature. Ether is added to the solution to saturation (75 milliliters). The solution is cooled to 10 C. and crystal- Elization induced by rubbing the sides of the reaction vessel with a glass rod. The product precipitates, the desired 1- (diethylamino )phenyl( 2-methylimidazol- 1 -yl )phosphine sul fide 3-methyl iodide, is separated by filtration and thereafter @dried. it is recrystallized twice, in the same manner, from a 1:4 methanol-ether solution; the product thus obtained melts at l94195 C. It has a specific rotation of [a] 70.3 (at a l concentration of 1.440 grams per 100 milliliters of ichloroform). A nuclear magnetic resonance spectrum of the icompound is identical with a nuclear magnetic resonance ispectrum obtained on an authentic sample of d!- l( diethylamino)phenyl(2-methyl-imidazol-1-yl)phosphine sulfide 3-methyl iodide which is prepared by reacting methyl iodide with dl-(diethylamino)-penyl(Z-methylimidazol-lyl)phosphine sulfide and found to possess the following structure. 4-t-butylphenoxy(2-methylimidazol-l-yl)phosphine sulfide 3- methylcamphorsulfonate has a specific rotation of [a] 28.10 (at a concentration of 1 .104 grams per 100 milliliters \il, methanol). Structure of the product is verified by nuclear F6. 19 magnetic resonance, infrared and elemental analyses. E

RESOLUTION (STEP II) EXAMPLE4 EXAMPLE6 The dl-( diethylamino)phenyl( 2-methylimidazoll -yl)phosphine sulfide 3 '-methyl a-d-camphorsulfonate product as obtained in example 1 is resolved to separate the less soluble diastereoisomer. More particularly, the compound is dissolved in 2 liters of benzene at a temperature of 50 C., with rapid stirring of the resulting solution. Thereafter, the solution is cooled to room temperature and crystallization induced by rubbing the side of the reaction vessel with a glass rod. The mixture is further cooled to 10 C. and held at that tempera- 6 ture for 10 hours, at which time the reaction mixture is filtered. The solid thus obtained is washed with 50 milliliters of benzene (at 10 C.) and thereafter dried to obtain a crystalline solid melting at 127130 C. The specific rotation of the substance is determined to be [oz],, "-i-0.65 (at a concentration of 1.854 grams per 100 milliliters of chloroform). The nuclear magnetic resonance spectrum is essentially identical with that obtained on the diastereoisomer mixture as prepared in example l. The solid is recrystallized from 1.8 milliliters of benzene, resulting in 17.1 grams of purified l- (diethylamino)phenyl(2methylimidazol-l-yl)phosphine sulfide 3-methyla-d-camphorsulfonate, melting at 132 C.

The specific rotation of this product is determined to be [a] ,,-3.14 (at a concentration of 1.752 grams per 100 milliliters of chloroform In analogy to the reaction described by this example other compounds of formula III are prepared by reacting acetonesoluble alkali metal iodides with appropriate complexes of formula II to give, for example, (diethylamino)2,4

55 dichlorophenoxy(2-methylimidazol-l-yl)-phosphine sulfide 3- methyl iodide", melting at 155-156 C.

PREPARATION OF COMPOUNDS OF FORMULA 1V EXAMPLE 7 -(Diethylamino)phenyl(2-methylimidazol-1-yl)phosphine sulfide 3-methyl iodide (2.0 grams; 0.00461 mole), a portion of the product as prepared in example 5 is mixed with milliliters of 1,2dimethoxyethane. The mixture is cooled to a temperature of 0 C. and maintained under nitrogen. Thereafter, 0.48 gram of lsodio-Z-methylimidazole (0.00461 mole) is added portion wise to the mixture over a period of 40 minutes. The resulting reaction mixture is maintained at 0 C. 0 for an additional 2 hours, at which time the solvent is removed by evaporation under subatmospheric pressure. The residue is mixed with milliliters of benzene and cooled to 10 C. and maintained thereat for a period of 1 hour. Thereafter, the mixture is filtered to remove sodium iodide and the filtrate ex- 5 tras smhfiyi uqs s ixs 0-m li itsa Portions of ice water This product residue is a thick syrup which partially solidified upon standing. lts specific rotation is [a],,+7.4 (at a concentration of 1.622 grams per 100 milliliters of chloroform). On standing in contact with l0 milliliters of cyclohexane at a temperature of C. for several hours, the product solidifies completely and is separated by filtration and thereafter dried. The product thus obtained is found to exist as a colorless crystalline solid melting at 8283 C. and having a specific rotation of [a] H-8.2 (at a concentration of 1.404 grams per 100 milliliters of chloroform), and of +5.6 (at a concentration of 1.376 grams per 100 milliliters of benzene). This optical isomer possesses the same degree of useful fungitoxicity as the racemic compound (SCIENCE 158, 1462 but is less than half as toxic to mammals than is the racemate, and, therefore, a practically more valuable plant fungicide.

EXAMPLE 8 cichoracearum and Phytophthora infestans, and other important plant fungi (SCIENCE 158, 1462).

EXAMPLE 9 A partial solution of 1.00 grams of l-(diethyl-amino)phenyl(Z-methylimidazol-l-yl)phosphine sulfide 3-methyl iodide (0.0023 mole) in 25 milliliters of 1,2-dimethoxyethane containing 0.168 gram of n-butylamine (0.0023 mole) is refluxed for 20 hours. The resulting mixture is evaporated to dryness 8 INVERSION or THE CONFIGURATION or ENANTIOMERS The inversion of the configuration of one enantiomer to the other configuration can be readily obtained. The inversion is more easily explained by the following reaction scheme levorotatory (loweralkyl) N-ZE-N l \Q aL e Step IV dextrorotatory (loweralkyl),Ni| -N loweralkyl under subatmospheric pressure and the remaining residue lwomtamry mixed with milliliters of benzene and filtered to remove 2,3-dimethylimidazole hydriodide byproduct. The filtrate is extracted with five successive 30 -milliliter portions of water, dried, and evaporated under subatmospheric pressure to obtain the desired d-(diethylamino)(n-butylamino)phenyl phos- 50 phine sulfide product as a residue. The product thus obtained is a colorless oil having a specific rotation of [0:] +1 7.2 (at a. concentration of 1.1 grams per 100 milliliters of chloroform). The substance is analyzed by nuclear magnetic resonance analysis and the spectrum thereby obtained found to be essentially identical with the nuclear magnetic resonance spectrum obtained on the racemic mixture of the same substance] prepared by reacting dl-(diethylamino )phenyl(2- methylimidazol-l-yl)phosphine sulfide 3 -methyl iodide with n-butylamine.

ln analogy to the reactions described in the preceding example and using the appropriate reactants as disclosed herein,. other compounds of formula IV are synthesized, for example:

(Ethylamino)(4-nitrophenoxy)(amino)phosphine sulfide;

having a density of 1.15 at 24 C. (Dimethylamino )(amino)( 2,4,5-trichlorophenoxy) phine sulfide; melting at l l9-l 20. (Dimethylamino methylamino 2 ,6-dicyclohexyl-4- phoss lowerelkyl Step IV EXAMPLE 10 A solution of 3.00 grams of d-(diethylamino)-phenyl(2- methylimidazol-lyl)phosphine sulfide (prepared as reported 1 hereinabove: example 7 in 15 milliliters of methyl iodide is allowed to stand at room temperature for 5 hours; during this period of time, a crystalline precipitate appears in the reaction 5 mixture. The precipitate, the expected d-(diethylamino)phenyl(2-methylimidazol-l-yl)phosphine sulfide 3 methyl iodide, is

separated by filtration and thereafter purified by recrystallization from a mixture of methanol and ether at room temperature. The product thus obtained melts at l94.0-l96.5 C. and l has a specific rotation of [a] +7l.5 (at a concentration of 1.8 grams per 100 milliliters of chloroform). The nuclear magnetic resonance spectrum of the product is essentially identical with the spectrum of its optical antipode (example 5 EXAMPLE 1 l i d-(Diethylamino)phenyl(2-methylimidazol-l-yl)phosphine sulfide 3-methyl iodide (3.40 grams; 0.00781 mole). (8 pmtion of the substance prepared in the preceding example) and methyl-phenoxy)phosphine sulfide;meltingat l74-l76. l-sodio2-methylimidazole (0.8l gram; 0.00780 mole) are (Dimethylamino N-methylanilino 2-chloro-4-t-butylhcnoxy)phosphine sulfide; having a molecular weight of 397.

(Dibutylamino)(Z-methylthio phenoxy)(amino) phosphine sulfide; having a molecular weight'of 346 reacted together as follows. The sodium salt is dispersed in l,2-dimethoxyethane (100 milliliters). The resulting dispersion is cooled to 0 C. and maintained under a nitrogen atmosphere. The phosphine sulfide methyl iodide is added to the 75 dispersion, portionwise-over a period of 1 hour at a temperature of 0 C. Thereafter, the reaction mixture is permitted to wherein R represents hydrogen or loweralkyl of one to four warm to room temperature, at which temperature it is held, Carbon atoms, inclusive; the term y represents an with stirring, for an additional 3 hours, and evaporated to drylky radical of one to foul Carbon atoms, inclusive; Y [was under subatmospheric pressure, h b b i i 3 represents an anion of an optically active camphorsulfonic residue. This residue is mixed with 50 milliliters of benzene 5 fffflflEEfjlQjjfif li lggl f Q fPl and filtered to separate sodium iodide byproduct. The W! Ri benzene filtrate is extracted with four successive l5 -milliliter portions of water, to remove 1,2-dimethylimidazole or byproduct, and dried over sodium sulfate and evaporated to u u dryness under subatmospheric pressure to obtain the desired l-( i hyl n )ph yl( -m yl l- -yDp osphine wherein R represents loweralkyl or cyclohexyl; R" represents sulfide product as a residue. This product residue, a thick, chloro, nitro or methyl mercapto; m represents an integer of colorless syrup, crystallized on standing in contact with 20 from 0 to 2, inclusive; n represents an integer of from 0 to 3,

milliliters of cyclohexane for several hours, at room temperainclusive; and the sum of m+n represents an integer of from 0 ture. The crystallized product melts at 8284 C. It is found to to 3, inclusive.

exhibit a specific rotation of [a],,9.3 (at a concentration of 2. A compound of claim 1 which is (diethylamino)-phen- 1.2 grams per 100 milliliters of chloroform). The nuclear magyl(2-methylimidazol-l-yl)phosphine sulfide 3-methyl a-dnetic resonance spectrum of the product is essentially identicamphorsulfonate. cal with the spectrum of the d-enantiomer (example 7 3. A compound of claim 2 in its dextrorotatory form. All of the compounds of the above examples (l-ll) have 4. A compound of claim 2 in its levorotatory form. been found to be effective pesticides. 5. A compound of claim 1 which is (diethylamino)-2,4- The compounds to be employed as starting materials in acdichlorophenoxy(2-methylimidazol-lyl)phosphine sulfide 3- cordance with the present invention: methyl camphorsulfonate.

' m T n w 6. A compound of claim 5 in its dextrorotatory form.

X N 7. A compound of claim 5 in its levorotatory form. (lowemlkyl) O 8. A compound of claim 1 which is (diethylamino )-2- chloro--4-t-butylphenoxy( 2-methylimidazol-l-yl)phosphine X sulfide 3-methyl camphorsulfonate.

9. A compound of claim 8 in its dextrorotatory form. 10. A compound of claim 8 in its levorotatory form.

are prepared by reacting an imidazole reactant:

i 11. A compound of claim 1 which is (diethylamino)-2,4-

1 l; dichlorophenoxy( 2-methylimidazol-l-yl)phosphine sulfide 3- N methyl a-d-camphorsulfonate.

12. A compound of claim 11 in its dextrorotatory form. with an appropriate phosphorus compound, which is of A PQW Q l in its levoromml'y form the following formula: 14. A compound of the formula X l lk l) N-i C1 l y 40 1owm1k 1 ,Ni*-N 0 i X 1|: \r .16 The reaction of imidazole reactant and phosphorus compound ILweralkyl is carried out in the presence of a hydrogen chloride acceptor and in the presence of an inert liquid reaction medium. The wherein R represents hydrogen or loweralkyl of one to four imidazole reactant can be employed as the hydrogen chloride carbon atoms, inclusive; the term loweralkyl" represents an acceptor. Good results are obtained when operating at temalkyl radical of one to four carbon atoms, inclusive; and X peratures of from 15 to 60 C. and when employing represents a radical oij the formula stoichiometric proportions of the reactants and of hydrogen chloride acceptor. R... R'm

The alkyl camphorsulfonates used as starting materials are all well-known compounds and can be conveniently prepared by the method taught in J. Chem. Soc. 97, pages 223-231 (1910) or J. Indian Chem. Soc. 35, pages 49-52 (1958), whereby equivalent amounts of an alkali metal alkyloxide is wherein R represents loweralkyl or cyclohexyl; R represents heated with an appropriate camphorsulfonyl halide in the chloro, nitro or methyl mercapto; m represents an integer of respective alcohol from 0 to 2, inclusive; n represents an integer of from 0 to 3, 'what is claimed is: inclusive; and the sum of m-l-n represents an integer of from 0 15. A compound of claim 14 which is (diethylamino)-phen- S yl( 2-methylimidazol-l-yl)phosphine sulfide 3-methyl-iodide. (1wem1ky1)N N O i Y9 16. A compound of claim 15 in its dextrorotatory form.

N 17. A compound of claim 15 in its levorotatory form.

M v loweralkyl as e w @2 3 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,621,031 Dated 16 November 1971 Invent fls) Henry Tolkmith James N. Seiber and Paul B. Budde It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column line h, delete "loweralkyl-y" and insert --lowere.lkyl'Y-.

line 6, delete "r" and insert -7f- Column 5, line "(2, change "132- C." to l32l33 C..

Signed and sealed this 26th day of September 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attestlng Officer Commissioner of Patents 

2. A compound of claim 1 which is (diethylamino)-phenyl(2-methylimidazol-1-yl)phosphine sulfide 3-methyl Alpha -d-camphorsulfonate.
 3. A compound of claim 2 in its dextrorotatory form.
 4. A compound of claim 2 in its levorotatory form.
 5. A compound of claim 1 which is (diethylamino)-2,4-dichlorophenoxy(2-methylimidazol-1-yl)phosphine sulfide 3-methyl camphorsulfonate.
 6. A compound of claim 5 in its dextrorotatory form.
 7. A compound of claim 5 in its levorotatory form.
 8. A compound of claim 1 which is (diethylamino)-2-chloro-4-t-butylphenoxy(2-methylimidazol-1-yl)phosphine sulfide 3-methyl camphorsulfonate.
 9. A compound of claim 8 in its dextrorotatory form.
 10. A compound of claim 8 in its levorotatory form.
 11. A compound of claim 1 which is (diethylamino)-2,4-dichlorophenoxy(2-methylimidazol-1-yl)phosphine sulfide 3-methyl Alpha -d-camphorsulfonate.
 12. A compound of claim 11 in its dextrorotatory form.
 13. A compound of claim 11 in its levorotatory form.
 14. A compound of the formula
 15. A compound of claim 14 which is (diethylamino)-phenyl(2-methylimidazol-1-yl)phosphine sulfide 3-methyl-iodide.
 16. A compound of claim 15 in its dextrorotatory form.
 17. A compound of claim 15 in its levorotatory form. 